The objectives of this study are: 1) to determine the contributions of active transport and passive distribution of ions across the blood-brain barrier to the regulation of brain extracellular fluid acid-base balance and 2) to assess the contribution of choroid plexus and central nervous system capillaries to this regulatory process. We have published experiments examining the distribution of H ion and HCO3- between CSF and blood during sustained arterial acid-base derangements in dogs and found evidence compatible with passive distribution for these ions if one assumes they are influenced by the pHa-dependent CSF-plasma DC electrical potential (PD). To examine this question further, in anesthetized ventilated dogs, we will measure the PD and CSF and plasma acid-base parameters during sustained changes in pHa under several experimental conditions: 1) Hypotherma to 27 degrees centigrade ATPase-dependent Na-K ion pumps and may help delineate betwen active and passive transport of H ion. 2) Elevations in plasma (K ion) increase the PD, which should influence the distribution of passively distributed ions, allowing us to examine regulation of CSF H ion in response to pHa changes but with the PD altered by another means. 3) Carbonic anhydrase inhibitor will be introduced into the CSF to examine the influence of carbonic anhydrase on the PD and on the distribution of H ion and HCO3-. 4) The sensitivity of the CSF-blood DC potential to changes in pHa will be measured in situ across the choroid plexus in the dog using microelectrode techniques. Its absence would suggest choroid plexus plays a different role in CSF acid-base regulation than the brain capillary network. 5) The PD will be measured between CSF and blood in humans who, for neurosurgical indications, have a CSF drain placed either in the lateral ventricle or lumbar spine.